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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 393, Issue 12

Issues

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

Jyotsna Batra
  • Corresponding author
  • Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Tracy O’Mara
  • Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
  • Molecular Cancer Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Radhika Patnala
  • Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Felicity Lose
  • Molecular Cancer Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Judith A. Clements
  • Corresponding author
  • Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2012-11-13 | DOI: https://doi.org/10.1515/hsz-2012-0211

Abstract

The Kallikrein (KLK) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

This article offers supplementary material which is provided at the end of the article.

Keywords: cancer; genome-wide association study; high-risk variants; imputation; kallikrein; single nucleotide polymorphism; tag single nucleotide polymorphism (SNP)

About the article

Jyotsna Batra

Dr Jyotsna Batra is an NHMRC Peter Doherty Fellow at Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, QUT. She has studied Biochemistry towards a Master’s degree at the Kurukshetra University, India in 2002. Jyotsna finished her PhD on Human genetics in 2008 from the Institute of Genomics and Integrative Biology, India, working on the complexity of the heredity allergic disorders. The focus of her current postdoctoral fellowship is to identify the molecular consequences of prostate cancer risk-associated single nucleotide polymorphisms (SNPs) already identified by GWAS and/or by fine mapping of the KLK3 gene, and to investigate novel Kallikrein gene SNPs extracted from Nextgen sequencing for an association with prostate cancer risk and/or prognostic features.

Tracy O’Mara

Tracy O’Mara graduated with a Bachelor of Applied Science (Life Sciences) with first class honours from the Queensland University of Technology (QUT) in 2005. From 2006–2008 she worked as a Research Assistant for Dr Mary-Anne Kedda from the School of Public Health and Institute of Health and Biomedical Innovation, QUT. Tracy began her PhD investigating the role of single nucleotide polymorphisms on endometrial cancer risk and aggressiveness in 2008 under the supervision of A/Prof Amanda Spurdle from the Queensland Institute of Medical Research and Prof Judith Clements from the Institute of Biomedical Innovation, QUT.

Radhika Patnala

Radhika Patnala completed her B.Tech Biotechnology from GITAM University, India in 2009 and graduated with Masters of Biotechnology (Honours) from the Australian National University, Canberra in 2011, under supervision of Dr Danny Rangasamy, John Curtin School of Medical Research. She then worked as a part time Research Assistant at Queensland University of Technology with Dr Jyotsna Batra. She will be pursuing doctoral research in the field of Neuroscience from August 2012 under A/Prof S Thameem Dheen at the Yong Loo Lin School of Medicine, National University of Singapore.

Felicity Lose

Felicity Lose completed her PhD from Queensland Institute of Medical Research in 2007 in cancer genetics. Since then, she have been involved in prostate cancer research, firstly as Project Co-ordinator for two large control recruitment projects (over 1200 controls recruited total), and now involved in genotyping and analysis of our large prostate cancer case and male control sample sets for the Kallikrein genes.

Judith A. Clements

BAppSc, RMIT, 1982; MAppSc, RMIT, 1983; PhD, Monash University, 1989.

Professor Judith Clements is an NHMRC Principal Research Fellow, Scientific Director of the Australian Prostate Cancer Research Centre-Queensland and leads the Cancer Program at the Institute of Health and Biomedical Innovation, Queensland University of Technology. Her research focuses on mechanistic and translational studies of the role of PSA and the related kallikrein serine peptidases in prostate cancer.


Corresponding authors: Jyotsna Batra and Judith A. Clements, Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia


Received: 2012-05-24

Accepted: 2012-07-30

Published Online: 2012-11-13

Published in Print: 2012-12-01


Citation Information: Biological Chemistry, Volume 393, Issue 12, Pages 1365–1390, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0211.

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